Antibodies reactive with Candida albicans mannoprotein are found in sera of most normal adults. Often referred to as "natural" antibodies, the amount of anti-mannan antibody found in a population of donors is normally distributed ; some individuals have little or not antibody, other individuals have remarkably high titers. Little is known about the fine epitope specificity or biological activity of naturally-occurring antimannan antibody. "Natural" antimannan IgG may be a first-line defenses against systemic Candida infection. The goal of the Candida: Protective Immunity MRU is to establish a knowledge base essential for development of a Candida vaccine. Naturally- occurring antimannan antibodies are a key issue that must be considered if active immunization, be it by a protein antigen (Edwards and Mitchell projects) or an epitope derived from a polysaccharide antigen (Cutler project), is to be successful. Moreover, the presence of these antimannan antibodies and the ability to affinity purify hundreds of milligrams of antibody from human plasma enables an evaluation of the function, including protective efficacy, of human antimannan antibodies. The central hypotheses is that naturally-occurring human antimannan antibodies have biological activities that influence host resistance to disseminated candidiasis. Moreover, these biological activities may be dependent on the epitope specificity of naturally occurring antimannan antibodies to activation of the classical and alternative complement pathways; iii) assess the opsonic activity of naturally-occurring antimannan antibodies; iv) determine whether naturally-occurring anti-Candida antibodies are productive in murine models of candiasis, and v) assess the effects of circulating "natural" antimannan antibodies on the efficacy of immunoprotective strategies developed by other components of the Mycology Research Unit.